PROJECT SUMMARY/ABSTRACT The objective of the proposed studies is to establish whether the rate and severity of post-traumatic osteoarthritis (PTOA) is related to joint motion abnormalities, and whether inferior in vivo anterior cruciate ligament (ACL) graft biomechanical properties are sufficient to induce joint motion abnormality. The ACL is the most frequently injured knee ligament. Surgical ligament reconstruction using a tendon graft is the gold standard treatment for an ACL tear, but the procedure does not restore normal joint motion completely and fails to prevent PTOA in many subjects. Why ACL reconstruction fails in these two regards is not completely understood. Much information from animal models and ex vivo experiments suggests that ACL graft function is inferior to that of the native ACL. The first mentored phase study will investigate the relationships between abnormal joint motion, long-term joint damage, and impaired graft function following ACL reconstruction in a clinical patient cohort. Accurate 3D knee joint motion during a hopping task will be recorded in a subset of patients and healthy controls enrolled an ongoing prospective clinical trial of ACL reconstruction outcomes (NCT 00434837). Cartilage and bone damage will be quantified from magnetic resonance (MR) images. We will estimate ACL graft stiffness from the MR image properties, and determine whether the abnormal joint motions are related to inferior graft stiffness in this clinical population. Using data from the longitudinal clinical trial will allow us to quantify joint damage progression between earlier time points and the 10-year follow-up, and to understand these structural changes in light of functional joint and ACL graft changes for the first time. However, different 3D anatomical structure and non-anatomical placement of the ACL graft also likely contribute to the residual abnormal joint motions we expect to observe clinically. Therefore, the second independent phase study will utilize an ACL reconstruction animal model and the same MR imaging techniques used in the mentored clinical study to investigate the time course of changes in ACL graft biomechanical properties while using the native ACL as the ?graft?. This technique simulates the important aspects of bone drilling and graft fixation in clinical ACL reconstruction, but circumvents the confounding effects of differences in anatomy and function between tendon graft and native ligament. ACL ?graft? biomechanical properties and joint motion will be assessed prior to ?reconstruction?, and then longitudinally for 20 weeks. The independent phase project will provide insight as to whether a threshold in ligament function exists that preserves joint motion. The translational design of the mentored and independent studies will address why the current gold standard ACL treatment fails to prevent PTOA, provide tools to monitor functional joint and tissue changes non-invasively, and provide targets for new treatment interventions.